The major objectives of this research are the development of a methodologic approach to assess sympathetic nervous system (SNS) activity and the application of this to an evaluation of the pathogenetic role of the SNS in the syndrome of essential hypertension. It is proposed that the SNS is one component of several genetically and environmentally determined factors which contribute to the development and sustenance of elevated arterial pressure. Evaluation of SNS activity in the basal state has led to conflicting data which have contributed little to a solution of this question. It is therefore proposed to assess SNS reactivity to several environmental variables which appear to influence blood pressure levels, namely reduction of extracellular fluid volume, alterations in caloric intake, and psychological stress. In order to obtain the most comprehensive quantification of SNS activity, it is planned to measure plasma levels of epinephrine and norepinephrine and the rate of urinary excretion of the major catecholamine metabolites, methoxyhydroxymandelic acid (VMA) and methoxyhydroxyphenyl glycol (MHPG). Studies will be done in the basal and reactive states. Volume depletion with diuretic therapy will be induced and the blood pressure response correlated with alterations in activities of the SNS and the renin-angiotensin system. The response of blood pressure and SNS activity to periods of overfeeding and of caloric deprivation will be examined in obese and non-obese hypertensives and compared to responses in obese and non-obese non-hypertensives. The acute reponse to imposed psychological stress will be measured in early, mild hypertension and related to the effects of anxiety-producing naturally occurring life events.